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Multicenter Study
. 2025 Jun 30;17(7):934.
doi: 10.3390/v17070934.

Adoptive JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy: Experience from Two Italian Centers

Maria Magdalena Pocora  1   2 , Paola Bini  3 , Giulia Berzero  4 , Elisa Vegezzi  3 , Luca Diamanti  3 , Matteo Gastaldi  3 , Paola Cinque  5 , Gaia Catalano  5   6 , Matteo Paoletti  7 , Anna Pichiecchio  1   7 , Fulvio Tartara  2 , Sabrina Basso  8   9 , Fausto Baldanti  10   11 , Milena Furione  10 , Patrizia Comoli  8   9 , Enrico Marchioni  3
Affiliations
Multicenter Study

Adoptive JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy: Experience from Two Italian Centers

Maria Magdalena Pocora et al. Viruses. .

Abstract

Background: Progressive multifocal leukoencephalopathy (PML) is a rare but fatal disease caused by John Cunningham virus (JCV) in immunocompromised individuals, with no effective antiviral treatment currently available. This study aimed to evaluate the feasibility of adoptive JCV-specific T lymphocyte therapy in patients with PML.

Methods: Nineteen patients meeting the 2013 consensus criteria for "definite PML" were included, and JCV-specific T lymphocytes expanded from autologous or allogeneic peripheral blood mononuclear cells (PBMCs) using JCV antigen-derived peptides were administered. Clinical outcomes were monitored through neuroimaging and biological markers.

Results: The mean age at diagnosis was 56.5 years, with a mean time to treatment of three months. Patients received a median of two infusions. At 12 months, six patients (31.6%) survived, while 13 (68.4%) had died, primarily due to PML progression. Survivors had a higher median baseline Karnofsky performance scale (KPS) score (50% vs. 30%, p = 0.41) and a significantly shorter diagnosis delay. MRI assessment showed a reduced disease burden in survivors, and JCV-DNA copy numbers decreased overall. One case of immune reconstitution inflammatory syndrome (IRIS) was observed.

Conclusions: Adoptive JCV-specific T lymphocytes may represent a safe therapeutic option for PML patients, and the MRI burden and JCV-DNA copy may serve as biomarkers for disease monitoring.

Keywords: JCV; adoptive T cell therapy; progressive multifocal leukoencephalopathy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of study design and inclusion/exclusion criteria. HIV = human immunodeficiency virus; PML = progressive multifocal leukoencephalopathy.
See this image and copyright information in PMC

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